Abstract The goal of the PDX Core is to provide high-quality, clinically relevant, and molecularly annotated PDX models for the research projects described in the University of Texas PDX Development and Trial Center (UTPDTC) grant application by leveraging PDX resources at our institutions and developing new PDX models using rigorous quality standards so that the models can be used to guide clinical trial development. Because of U54 funding limitations and to keep things as simple as possible, this U54 PDX Core will only function at the MD Anderson Cancer Center which has more than enough surgical specimens coming in to fulfill the needs of this grant. The existing UTSW PDX lung cancer models (~40) developed through the NCI SPORE in Lung Cancer (P50CA70907) will be used by UTSW in Project 1, and new and existing UTMDACC PDX models created by the PDX Core at MDACC will be supplied to the various projects including for the UTSW component of Project 1. The PDX models developed and/or characterized under this UTPDTC grant will be available to other cancer researchers through the NCI Patient-Derived Models Repository and PDX Development and Trial Centers Research Network (PDXNet). We are in a unique position to provide high-quality PDX models for studies described in this grant application and for the cancer research community. Our research team has established 506 PDX models from human lung, breast, colorectal, and pancreatic cancers and completed whole exome sequencing and RNA sequencing for 176 and 94 of these models respectively. We are currently participating in the NCI's collaborative initiative on PDX models through two separate NCI supplemental awards. We will use the rigorous quality standards developed by the NCI to generate and characterize PDX models and provide high- quality PDX models for preclinical investigations. Furthermore, we will enhance the diversity of PDX models for answering clinical and/or translational questions by leveraging the world-class translational expertise and access to human tissues unique to our institutions for generating new PDX models. For example, more than 20,000 surgical procedures and 50,000 diagnostic and/or treatment procedures are performed annually at UTMDACC. Our patient consent forms have already been reviewed by NCI staff and are appropriate for sharing PDXs with the cancer research community through NCI's Patient-Derived Models Repository and PDXNet. To achieve our goal of supporting the UTPDTC projects and PDXNet activities, we will provide high-quality clinically and molecularly annotated PDXs after rigorous quality testing of established PDX models and enhance the diversity of PDX models by generating and characterizing new models. The proposed study has significant public health implications because providing the highest quality PDX models for the preclinical investigations described in this application and to the cancer research community will ultimately improve and accelerate the development of new effective biomarker-driven cancer therapies, helping cancer patients fight their disease.